Disruption of Endogenous Damage Receptor Signaling to Improve Performance of Intracortical Microelectrodes

摘要

Removal of endogenous damage receptor signaling pathways effectively reduced inflammation in response to an implanted intracortical mictroelectrodes. However the downstream consequences of each specific pathway are not uniform. For example, Tlr2~(-/-) mice, missing a receptor involved in the recognition of necrotic cell debris, had a more stable blood-brain barrier and reduced microglial activation, but did not demonstrate reduced neuronal dieback around the implant site. Tlr4~(-/-) mice, missing a receptor involved in the recognition of serum proteins, did not exhibit any significant improvements beyond microglial activation. Cd14~(-/-) mice, missing a co-factor to both TLR2 and TLR4 signaling pathways, demonstrated reduced astrocytic scarring and neuronal dieback relative to wildtype mice. Thus, Cd14~(-/-) mice were chosen for ongoing functional recording studies. The reduction in neuronal dieback in Cd14~(-/-) mice may translate to higher quality signals and improved stability in the long term. In addition, the reduced astrocytic scarring may also translate to reduced recording impedance.